Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A molecular docking investigation has been carried out on cytotoxic prenylated flavonoids from Lonchocarpus haberi with cancer-relevant chemotherapeutic targets known to be inhibited by flavonoids. Two molecular docking programs, Molegro and ArgusDock, were used to compare the binding energies of Lonchocarpus flavonoids with other flavonoids, inhibitors, or known ligands, to aromatase (CYP 19), fatty acid synthase (FAS), xanthine oxidase (XO), cyclooxygenases (COX-1 and COX-2), lipoxygenase (LOX-3), ornithine decarboxylase (ODC), protein tyrosine kinase (PTK), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), topoisomerase II (ATP binding site), ATP binding cassette (ABC) transporter, and phospholipase A(2) (PLA). The Lonchocarpus flavonoids examined in this study exhibited docking energies comparable to or stronger than other flavonoids that had been previously shown to be effective inhibitors of these enzymes. Furthermore, prenylated flavonoids, such as the Lonchocarpus flavonoids and xanthohumol, generally showed greater binding energies than the non-prenylated flavonoids. We conclude, therefore, that the Lonchocarpus flavonoids possibly owe their cytotoxic activity by inhibition of one or more of these enzymes.
J Mol Model 2010 Feb
PMID:Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis. 1960 3

The molecular basis of the human group IIA secretory phospholipase A(2) inactivation by bolinaquinone (BLQ), a hydroxyquinone marine terpenoid, has been investigated for the comprehension of its relevant antiinflammatory properties, through the combination of spectroscopic techniques, biosensors analysis, mass spectrometry (MS) and molecular docking. Indeed, sPLA(2)s are well known to be implicated in the pathogenesis of inflammation such as rheumatoid arthritis, septic shock, psoriasis and asthma. Our results suggest a mechanism of competitive inhibition guided by a non-covalent molecular recognition event, disclosing the key role of the BLQ hydroxyl-quinone moiety in the chelation of the catalytic Ca(2+) ion inside the enzyme active site.The understanding of the sPLA(2)-IIA inactivation mechanism by BLQ could be useful for the development of a new chemical class of PLA(2) inhibitors, able to specifically target the enzyme active site.
J Mol Recognit
PMID:The molecular mechanism of human group IIA phospholipase A2 inactivation by bolinaquinone. 1962 21

We have developed a mulch sheet made by inflation molding of PLA, Ecoflex((R)) and modified starch, which all have different biodegradabilities. A field test of use as an agricultural mulch sheet for mandarin oranges was carried out over two years. The mechanical properties of the mulch sheet were weakened with time during the field test, but the quality of the mandarin oranges increased, a result of the controlled degradation of the sheet. The most degradable modified starch degraded first, allowing control of the moisture on the soil. Accelerator mass spectroscopy was used for evaluation of the biomass carbon ratio. The biomass carbon ratio decreased by degradation of the biobased materials, PLA and modified starch in the mulch sheet.
Int J Mol Sci 2009 Aug 17
PMID:Utilization of a biodegradable mulch sheet produced from poly(lactic acid)/ecoflex/modified starch in mandarin orange groves. 1981 15

Anaerobic biodegradation tests of poly(lactic acid) (PLA) powder were done at the thermophilic (55 degrees C) and mesophilic temperature (35 degrees C) under aquatic conditions [total solid concentrations of the used sludge were 2.07% (at 55 degrees C) and 2.24% (at 35 degrees C)] using a newly developed evaluation system. With this system, the evolved biogas is collected in a gas sampling bag at atmospheric pressure. This method is more convenient than using a pressure transducer or inverted graduated cylinder submerged in water. PLA was degraded about 60% in 30 days, about 80% in 40 days and about 90% in 60 days at 55 degrees C. On the other hand, the PLA degradation started in 55 days at 35 degrees C and degradation rate was much slower than at 55 degrees C.
Int J Mol Sci 2009 Sep 02
PMID:Anaerobic biodegradation tests of poly(lactic acid) under mesophilic and thermophilic conditions using a new evaluation system for methane fermentation in anaerobic sludge. 1986 21

Plasmalogen-selective phospholipase A(2) (PlsEtn-PLA(2)) has been purified from pig brain using multiple column chromatographic procedure. The purified enzyme migrates as a single band on polyacrylamide. It is stimulated by Triton X-100 and inhibited by sodium deoxycholate. Purified PlsEtn-PLA(2) is inhibited by iodoacetate, and this inhibition can be prevented by beta-meracaptoethanol. Treatment of neuronal cell cultures with kainic acid stimulates PlsEtn-PLA(2) activity in a dose-dependent manner, and this stimulation can be blocked by Ly294486, a selective kainic acid receptor antagonist. Activities of PlsEtn-PLA(2) are markedly increased in plasma membrane and synaptosomal plasma membrane fraction prepared from nucleus basalis and hippocampal region of brains from Alzheimer disease patients compared to age-matched controls. It is proposed that accumulation of ceramide and increased expression of cytokines may be responsible for the stimulation of PlsEtn-PLA(2) in Alzheimer disease.
Mol Neurobiol 2010 Jun
PMID:Studies on plasmalogen-selective phospholipase A2 in brain. 2004 56

Biodegradabilities of polymers and their composites in a controlled compost were described. Polycaprolactone (PCL) and poly(lactic acid) (PLA) were employed as biodegradable polymers. Biodegradabilities of PCL and PLA samples in a controlled compost were measured using a Microbial Oxidative Degradation Analyzer (MODA) according to ISO 14855-2. Sample preparation method for biodegradation test according to ISO/DIS 10210 was also described. Effects of sizes and shapes of samples on biodegradability were studied. Reproducibility of biodegradation test of ISO 14855-2 by MODA was confirmed. Validity of sample preparation method for polymer pellets, polymer film, and polymer products of ISO/DIS 10210 for ISO 14855-2 was confirmed.
Int J Mol Sci 2009 Aug 18
PMID:Biodegradability evaluation of polymers by ISO 14855-2. 2011 76

Phospholipases A(2) (PLA(2)s) are a diverse family of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor which have been implicated in pathological states of numerous acute and chronic neurological disorders. To date, more than 27 isoforms of PLA(2) have been found in the mammalian system which can be classified into four major categories: secretory PLA(2), cytosolic PLA(2), Ca(2+)-independent PLA(2), and platelet-activating factor acetylhydrolases. Multiple isoforms of PLA(2) are found in the mammalian spinal cord. Under physiological conditions, PLA(2)s are involved in diverse cellular responses, including phospholipid digestion and metabolism, host defense, and signal transduction. However, under pathological situations, increased PLA(2) activity, excessive production of free fatty acids and their metabolites may lead to the loss of membrane integrity, inflammation, oxidative stress, and subsequent neuronal injury. There is emerging evidence that PLA(2) plays a key role in the secondary injury process after traumatic spinal cord injury. This review outlines the current knowledge of the PLA(2) in the spinal cord with an emphasis being placed on the possible roles of PLA(2) in mediating the secondary SCI.
Mol Neurobiol 2010 Jun
PMID:Phospholipase A2 and its molecular mechanism after spinal cord injury. 2012 25

The bioresponsive conjugate dextrin-phospholipase A2 (PLA2) is a novel anticancer polymer therapeutic. Dextrin conjugation decreases PLA2 bioactivity, but this can be restored following triggered degradation by alpha-amylase. The conjugate displays reduced hemolytic activity but retains, or shows enhanced, cytotoxicity in vitro that partially correlates with epidermal growth factor receptor (EGFR) expression. Here, we investigate further the mechanism of action of dextrin-PLA2 with the aim of judging its potential for combination with tyrosine kinase inhibitors (TKI) and/or chemotherapy and selecting the first models for in vivo evaluation. The endocytic fate of Oregon Green (OG)-labeled probes was assessed in MCF-7 cells. Whereas PLA2-OG showed greatest membrane binding, the dextrin-PLA2-OG conjugate displayed higher internalization. Moreover, cells incubated with PLA(2)-OG and dextrin-PLA2-OG showed an altered pattern of intracellular vesicle distribution compared to dextrin-OG. When cell lines known to express different levels of EGFR were used to assess cytotoxicity, free PLA2 activity was enhanced by addition of EGF whereas the conjugate was less cytotoxic, perhaps due to differences in their PK/PD profile. Co-incubation of cells with the TKI inhibitor, gefitinib, led to reduced cytotoxicity of both PLA2 and dextrin-PLA2 suggesting a TK-mediated PLA2 mechanism of action. However, the enhanced cytotoxicity seen in the presence of doxorubicin suggested potential for development of a dextrin-PLA2/doxorubicin combination therapy.
Mol Pharm 2010 Apr 05
PMID:Studies on the mechanism of action of dextrin-phospholipase A2 and its suitability for use in combination therapy. 2016 58

Alzheimer's disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Abeta) impact oxidative stress have not been adequately investigated. Recent studies provide strong evidence for the involvement of NADPH oxidase and its downstream oxidative signaling pathways in the toxic effects elicited by Abeta. ROS produced by NADPH oxidase activate multiple signaling pathways leading to neuronal excitotoxicity and glial cell-mediated inflammation. This review describes recent studies demonstrating the neurotoxic effects of Abeta in conjunction with ROS produced by NADPH oxidase and the downstream pathways leading to activation of cytosolic phospholipase A(2) (PLA(2)) and secretory PLA(2). In addition, this review also describes recent studies using botanical antioxidants to protect against oxidative damage associated with AD. Investigating the metabolic and signaling pathways involving Abeta NADPH oxidase and PLA(2) can help understand the mechanisms underlying the neurodegenerative effects of oxidative stress in AD. This information should provide new therapeutic approaches for prevention of this debilitating disease.
Mol Neurobiol 2010 Jun
PMID:Targeting NADPH oxidase and phospholipases A2 in Alzheimer's disease. 2019 96

Secretory phospholipase A(2) is involved in inflammatory processes and was previously shown to be inhibited by lipophilic tetracyclines such as minocycline (minoTc) and doxycycline. Lipophilic tetracyclines might be a new lead compound for the design of specific inhibitors of secretory phospholipase A(2), which play a crucial role in inflammatory processes. Our X-ray crystal structure analysis at 1.65 A resolution of the minoTc complex of phospholipase A(2) (PLA(2)) of the Indian cobra (Naja naja naja) is the first example of nonantibiotic tetracycline interactions with a protein. MinoTc interferes with the conformation of the active-site Ca(2+)-binding loop, preventing Ca(2)(+) binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. MinoTc binding to PLA(2) is dominated by hydrophobic interactions quite different from antibiotic recognition of tetracyclines by proteins or the ribosome. The affinity of minoTc for PLA(2) was determined by surface plasmon resonance, resulting in a dissociation constant K(d)=1.8 x 10(-)(4) M.
J Mol Biol 2010 Apr 23
PMID:Nonantibiotic properties of tetracyclines: structural basis for inhibition of secretory phospholipase A2. 2021 Nov 88


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